Diagnostic Device

ABSTRACT

Diagnostic devices for detecting the presence of an analyte in a sample are provided. Devices of the present invention comprise a means for inducing a pressure differential on a sample to direct the sample to a test surface. In one embodiment, the means for inducing a pressure differential on a sample to direct the sample to a test surface comprises a syringe that can be used to draw a sample from an opening to a test surface. In other embodiments, the device also provides means for diluting a sample. In yet other embodiments, the device also provides a means

FIELD OF THE INVENTION

The present invention relates to diagnostic devices. Particularly, thepresent invention relates to devices that comprise a means for inducinga pressure differential on a sample to direct the sample to a testsurface.

BACKGROUND

Diagnostic devices are used to detect an analyte in a sample. Thepresent invention relates to diagnostic devices and methods. In oneparticular embodiment, the present invention relates todiffraction-based diagnostic devices that can be used to detect one ormore analytes present in a medium by detecting diffraction of ananalyte/binder complex. These diffraction-based devices comprise asurface upon which is printed in a pattern a binder. Upon attachment ofanalyte to the binder that is printed in a pattern on the surface,diffraction of light that is transmitted through or reflected off of theprinted surface occurs via the physical dimensions and defined placementof the binder.

U.S. Pat. No. 4,992,385 to Godfrey, et al. describes a method ofpreparing a diffraction grating from a thin polymer film for subsequentuse as a sensing device. The sensing device described in U.S. Pat. No.4,992,385 requires the use of a spectrophotometric technique to detectchanges in the device's optical properties due to analyte binding. Thedevice and method described in U.S. Pat. No. 4,992,385 require a complexdetection method to detect changes in the diffraction pattern becausechanges in a diffraction pattern are more subtle than the qualitativedetermination that is made to determine whether a diffraction image isformed or is not formed.

U.S. Pat. No. 5,196,350 to Backman et al. describes an optical detectionmethod for detecting the presence of specific ligands. The methoddescribed in U.S. Pat. No. 5,196,350 is an optical detection method fordetecting specific ligands that requires a mask comprising slits toproduce a diffraction pattern. An immunoassay device is placed betweenthe mask and light source, so that binding by an analyte causes a changein the diffraction or interference pattern caused by the mask. Again,this method also requires a complex detection method to detect changesin a diffraction pattern and confirm the presence of a ligand.

International Publication No. WO 94/13835 describes a method and asystem to detect biological macromolecules via diffraction of light froma probe of predetermined dimensions that diffracts light in a knownpattern. The probe comprises an active surface that is able to highlyconcentrate the macromolecules relative to their concentration in thesample solution. The method and the system described in WO 94/13835 alsorequire the use of a complex detector and an analyzer in order to detectchanges in the diffraction pattern produced by the probe.

U.S. Pat. No. 6,261,519 describes a diagnostic device for measuring theconcentration of an analyte in a sample. The device comprises sampleport at one end for introducing a sample. The device also comprises abladder at the other end that must be depressed, inserted into a liquidsample and released to draw a sample. The device described in U.S. Pat.No. 6,261,519 does not further draw the sample passed a test site toclear the test site so that diffraction or non-diffraction at the testsite can be determined.

The methods, systems and devices discussed above do not provide a meansfor directing a sample to a test surface and then clearing the testsurface of sample so that diffraction or non-diffraction can bedetermined. Furthermore, the prior art fails to provide a device inwhich a user of the device can control the position of a sample with inthe device. What is needed is a simple, easy to use method, system anddevice for detecting an analyte that provides a means for directing asample to a test surface and then clears the test surface of enoughsample so that diffraction, and binding, can be accurately determinedand allows a user of the device to control movement and incubation orreaction time of a sample within the device.

SUMMARY OF THE INVENTION

The present invention provides diagnostic devices comprising a means forinducing a pressure differential on a sample to direct the sample to atest surface. In one embodiment, the means for inducing a pressuredifferential on a sample to direct the sample to a test surfacecomprises a syringe or a piston for pushing or pulling a fluid sample tothe test surface. In one embodiment, the diagnostic device is adiffraction-based diagnostic device and the means for inducing apressure differential on a sample to direct the sample to a test surfacealso further directs the sample past the test surface and removes mostof the sample from the test surface so that the test surface can beobserved by an individual or read by an analyzer. In a desirableembodiment, the test surface is located on a test strip that can beremoved from the device and observed by an individual or inserted intoan analyzer.

Features, aspects and advantages of the present invention will becomebetter understood with reference to the following description and theappended claims. The accompanying drawings, which are incorporated inand constitute a part of this specification, illustrate several examplesof the invention and, together with the description, serve to explainthe principles of this invention.

BRIEF DESCRIPTION OF THE FIGURES

The invention is hereinafter more particularly described by way ofexamples with reference to the following drawings in which:

FIG. 1 is a top view of a diagnostic device that includes apressure-assisted means for directing a sample to a test surface.

FIG. 2 is a side view of the diagnostic device.

FIG. 3 is a cross-sectional view of the diagnostic device taken throughline 3-3 of FIG. 2.

FIG. 4 is a top view of a diagnostic test strip separated from thedevice.

FIGS. 5, 6 and 7 are cross-sectional views of the diagnostic devicetaken through line 3-3 of FIG. 2 in various stages of operation of thepressure-assisted means.

FIG. 8 is a top view of the diagnostic device after operating thepressure-assisted means.

FIG. 9 is a top view of the diagnostic device illustrating one mode ofremoval of a removable test strip.

FIG. 10 is a side view of the removed test strip.

Repeated use of reference characters in the present application anddrawings is intended to represent the same, similar or analogousfeatures or elements of the invention.

DETAILED DESCRIPTION

Although the present invention is described in the context of severalspecific examples, configurations and embodiments, it will beappreciated that further combinations or alterations of the examples,configurations and embodiments illustrated herein and described hereinmay be made by one skilled in the art without departing from the spiritand scope of the present invention. In addition, although reference isoften made with respect to diffraction-based diagnostic devices, methodsand systems for detecting a protein, those skilled in the art willappreciate that other modifications may be made to adapt the diagnosticdevices, methods and systems for use with non-diffraction baseddiagnostic devices, methods and systems and for detecting analytes otherthan proteins. In the following discussion, reference is made to severalfigures to illustrate a few specific examples and embodiments of thepresent invention.

The present invention provides a diagnostic device that comprises ameans for inducing a pressure differential on a sample to direct thesample to a test surface. The means for inducing a pressure differentialon a sample to direct the sample to a test surface may direct all or aportion of the sample to the test surface. In addition, the means forinducing a pressure differential on a sample to direct the sample to atest surface also further directs the sample past the test surface toremove excess or unreacted sample from the test surface and may includeadditional means or structures to do so. Desirably, the sample isdirected past the test surface after the sample or a portion of thesample has become bound, reacted or otherwise interacted with the testsurface.

One embodiment of the present invention provides a device and method fordirecting a sample to a diffraction-based test surface and is describedand illustrated herein. For example, a diffraction-based diagnosticdevice can be used to direct a liquid sample, such as blood, to adiffraction-based test surface that tests for one or more analytes suchas a protein, such as C-reactive protein, IgE antibodies and so forth.

Examples of methods, systems and devices for detecting an analyte viathe formation of a diffraction image are disclosed and described in U.S.Pat. No. 5,922,550, U.S. Pat. No. 6,020,047, U.S. Pat. No. 6,221,579 andInternational Publication No. WO 98/27417 which are hereby incorporatedby reference herein in their entirety. The devices described in theabove-referenced documents can be produced by printing a species onto asurface. The species is selected to bind, react or otherwise associatewith an analyte of interest and is referred to herein as a “binder”. Abinder may include any chemical species, compound, composition, moiety,particle and so forth that will bind, react or otherwise associate withthe analyte of interest. Preferably, the binder is specific to theanalyte of interest or a class of analytes of interest and does notappreciably bind, react or otherwise associate with any other matterthat may be found in the sample of interest. The binder can be anyanalyte-specific receptor material that can be printed onto a substrateand that will specifically bind to an analyte of interest.

Thus, the binder is one part of a specific binding pair with theanalyte; examples of analyte/binder pairs include, but are not limitedto: antigen/antibody, such as IgE antibody/anti-IgE antibody;antibody/antibody-binding protein (e.g., Protein A or Protein G);enzyme/substrate; oligonucleotide/DNA; chelator/metal; enzyme/inhibitor;bacteria/receptor; bacteria/antibody to bacterial cell markers; orbacteria/anti-CRP antibody; virus/receptor or Influenza A andanti-Influenza A antibodies; fungus/anti-Aspergillus antibody; cellulartoxin/receptor; cellular toxin/antibody to toxin; fungus/receptor;hormone/receptor; DNA/RNA, or RNA/RNA; oligonucleotide/RNA; and bindingof these species to any other species, as well as the interaction ofthese species with inorganic species. The binder material that isprinted onto the substrate is characterized by an ability tospecifically bind the analyte or analytes of interest. The variety ofmaterials that can be used as a binder material are limited only by thetypes of material which will combine selectively (with respect to anychosen sample) with the analyte. Sub-classes of materials which can beincluded in the overall class of receptor materials includes toxins,antibodies, antigens, hormone receptors, parasites, cells, haptens,metabolites, allergens, nucleic acids, nuclear materials,autoantibodies, blood proteins, cellular debris, enzymes, tissueproteins, enzyme substrates, coenzymes, neuron transmitters, viruses,viral particles, microorganisms, proteins, saccharides, chelators,drugs, and any other member of a specific binding pair. This list onlyincorporates some of the many different materials that can be printedonto the substrate to produce a diagnostic device. Whatever the selectedanalyte of interest is, the binder is designed to bind, react orotherwise associate with the analyte(s) of interest.

Generally, the binder is printed onto a substrate, for example a plasticfilm, in a defined pattern such that the binder-printed film does notdiffract electromagnetic radiation when the electromagnetic radiation isreflected off of or transmitted through the binder-printed film butdiffracts electromagnetic radiation after the binder-printed film isexposed to the analyte and the analyte has bound, reacted or otherwiseassociated with the binder. Alternatively, the binder-printed film orsurface may exhibit a measurable increase or decrease in diffractionafter exposure to the analyte. For example, a film may be printed with abinder such that the binder-printed film does not diffract light butdoes diffract after an analyte binds, associates or otherwise reactswith the binder-printed surface. In another example, the binder-printedfilm initially diffracts light but does not diffract light or diffractsless after an analyte binds, associates or otherwise reacts with thebinder-printed surface. In yet another example, the film may be printedwith a binder so that binder-printed film initially diffracts light butwhen the analyte binds with binder-printed surface, light is diffractedto a measurably greater extent. Thus, the presence of analyte can bedetermined by a measurable change in diffraction of light that istransmitted through or reflected off of the substrate surface. If lightor other electromagnetic radiation is to be transmitted through thesurface of a film to detect diffraction, it is desirable that the filmis transparent or at least partially transparent to the light or otherelectromagnetic radiation that will be used to detect diffraction.

Devices of the present invention include a surface or at least a portionof a surface that is printed with a binder. The printing of the surfacemay be accomplished by microcontact printing the binder onto the surfacein a defined pattern. Microcontact printing is desirable and allowsprinting of patterns with size features of about 100 μm and smaller.Features in this size range are desirable for diffraction when theelectromagnetic radiation wavelength is in the spectrum of visiblelight, from about 4000 Angstroms to 7000 Angstroms. However, it is notedthat light over other wavelengths, both longer and shorter wavelengthelectromagnetic radiation, may be used to detect diffraction. A patternof binder allows for the controlled attachment of analyte or analytereceptor. An elastomeric stamp may be used to transfer binder to asurface. If the stamp is patterned, a patterned binder layer will beprinted on the surface when the stamp is wet with the binder, dried, andthen contacted with the surface.

Gold-coated, printed films that produce diffraction patterns and methodsof contact printing such films are described and disclosed in U.S. Pat.No. 6,020,047 and U.S. Pat. No. 6,048,623, which are hereby incorporatedby reference herein in their entirety. U.S. Pat. Nos. 6,020,047 and6,048,623 describe methods of microcontact printing self-assemblingmonolayers that allow for the selective placement of reagents that canreact chemically or physically with an analyte or a group of analytesthat are of interest to produce a diffraction image.

Generally, an analyte may be any stimulus including but not limited toany chemical or biological species, compound, composition, moiety,particle, and so forth that that will bind, react or otherwise associatewith the binder or with which the binder will respond. Analytes that arecontemplated as being detected include, but are not limited to, one ormore the following: species of bacteria, including, but not limited to,Hemophilis, Neisseria meningitides serogroups A, B, C, Y and W135,Streptococcus pneumoniae; yeasts; fungi; viruses including, but notlimited to, Haemophilus influenza type B or RSV; rheumatoid factors;antibodies including, but not limited to, IgG, IgM, IgA and IgEantibodies; antigens including, but not limited to, streptococcus GroupA antigen, streptococcus Group B antigen, viral antigens, fungalantigens, an antigen derived from microorganisms, antigens associatedwith autoimmune diseases, influenza and tumors; allergens; enzymes;hormones; saccharides; proteins, such as C-reactive protein (CRP);lipids; carbohydrates; drugs including, but not limited to, drugs ofabuse and therapeutic drugs, nucleic acids; haptens, environmentalagents, other blood-born disease markers; and so forth.

A binder may be microprinted on a polymer film or other substrate.Desirably, a binder is selected and printed that is an analyte-specificreceptor material and specifically binds to the analyte or class ofanalytes of interest. Thus, the binder material and analyte are definedas a specific binding pair with the analyte; examples of analyte/binderpairs include, but are not limited to, antigen/antibody,antibody/antibody-binding protein, enzyme/substrate,oligonucleotide/DNA, chelator/metal, enzyme/inhibitor,bacteria/receptor, virus/receptor, cellular toxin/receptor,fungus/receptor, hormone/receptor, DNA/RNA, or RNA/RNA,oligonucleotide/RNA, and binding of these species to any other species,as well as the interaction of these species with inorganic species. Thebinder material that is printed on to a substrate layer is characterizedby an ability to specifically bind the analyte or analytes of interest.The variety of materials that can be used as a binder material arelimited only by the types of material which will combine selectively(with respect to any chosen sample) with the analyte.

Subclasses of materials which can be included in the overall class ofbinder materials include toxins, antibodies, antigens, hormonereceptors, parasites, cells, haptens, metabolites, allergens, nucleicacids, nuclear materials, autoantibodies, blood proteins, cellulardebris, enzymes, tissue proteins, enzyme substrates, coenzymes, neurontransmitters, viruses, viral particles, microorganisms, proteins,saccharides, chelators, drugs, and any other member of a specificbinding pair.

U.S. Pat. No. 6,180,288 and International Publication No. WO 98/43086disclose and describe the use of one or more responsive gels coated on apatterned self-assembling monolayer and the use of such devices. Theresponsive gels described therein react or respond to a stimulus, i.e.an analyte, to produce a diffraction image. U.S. Pat. No. 6,180,288 andInternational Publication No. WO 98/43086 are both hereby incorporatedby reference herein in their entirety.

Diffraction-based detectors and methods of detection using opticaldiffraction that do not require self-assembled monolayers are disclosedand described in U.S. Pat. No. 6,060,256 and International PublicationNo. WO 99/31486. U.S. Pat. No. 6,060,256 and International PublicationNo. WO 99/31486 are hereby incorporated by reference herein in theirentirety. U.S. Pat. No. 6,060,256 and International Publication No. WO99/31486 also disclose and describe the optional addition of nutrientsfor a specific class of microorganisms with such diagnostic devices,systems and methods to provide for the detection of lower concentrationsof analytes.

U.S. Pat. No. 6,221,579 and International Publication No. WO 00/34781disclose and describe the addition of diffraction enhancing elements.Diffraction enhancing element particles that may be used with thepresent invention include, but are not limited to, glass, cellulose,synthetic polymers or plastics, latex, polystyrene, polycarbonate,bacterial or fungal cells, metallic sols, and so forth. A desirableparticle size ranges from a diameter of approximately 0.05 μm to 100.0μm. The composition of the element particle and structural and spatialconfiguration of the particle is not critical to the present invention.However, it is desirable that the difference in refractive index betweenthe medium and the enhancing element is between 0.1 and 1.0. Diffractionenhancing elements are optionally included in such devices, systems andmethods to provide for the detection of smaller species of analyte, suchas proteins, DNA, RNA, other low molecular weight analytes and lowmolecular weight surface markers on organisms. U.S. Pat. No. 6,221,579and International Publication No. WO 00/34781 describe the modificationof microspheres so that the microspheres are capable of binding with atarget analyte and to the device surface. The microspheres are capableof producing a substantial change in height and/or refractive index toenhance diffraction, thereby increasing the efficiency of such devices,systems and methods and can provide for the detection of smaller speciesof analyte. U.S. Pat. No. 6,221,579 and International Publication No. WO00/34781 are hereby incorporated by reference herein in their entirety.

International Publication No. WO 00/36416 describes and disclosesdevices and systems comprising a patterned deposition ofantibody-binding proteins for detecting antibodies. InternationalPublication No. WO 00/36416 is also hereby incorporated by referenceherein in its entirety.

FIG. 1 is a topside view of the exterior of device 100. In theembodiment illustrated in FIGS. 1-10, the device 100 comprises a housing20 and a test strip 40. A top view of test strip 40 is illustrated inFIG. 4. To provide a diffraction-based diagnostic test and device, teststrip 40 includes a test surface 42 on to which a binder 44 is printedin a defined pattern (not illustrated). Diffraction-based test methodsand devices for detecting one or more analytes are described in detailin the above-referenced patents and patent applications. Persons ofskill in the art will recognize that other test strips and test methodsmay be used with the present invention.

FIG. 2, is left side view of device 100. FIG. 3, is a cross-sectionalview of device 100 taken through line 3-3 of FIG. 2. In this illustratedembodiment, the device 100 is sealingly attached to a removable teststrip 40 to form a chamber 30 into which a sample can be directed sothat sample may contact test strip 40 and test surface 42. The housing100 further comprises an opening 22 for receiving a sample and a channel24 connecting the opening 22 to chamber 30 so that sample may bedirected from opening 22 to chamber 30. In another embodiment, theopening 22 may further comprise a collection pad onto which a sample maybe placed or otherwise deposited for testing. For example, an individualmay contact a freshly lanced finger or other body part to the collectionpad to deposit a blood sample for testing within the device 100. Thecollection pad and opening 22 are in fluid communication and connectedto chamber 30 via channel 24. The sample can be directed from theopening 22 to test surface 44 by operating the means for inducing apressure differential on a sample to direct the sample to a testsurface. The means for inducing a pressure differential on a sample todirect the sample to a test surface may be any means that can be used todirect, force, urge or otherwise compel a sample from one location toanother location.

In the embodiments illustrated in FIGS. 1-10, the means for inducing apressure differential on a sample to direct the sample to a test surfaceis a syringe or a syringe-like device, illustrated generally as 50.Exemplary means for inducing a pressure differential on a sample todirect the sample to a test surface include any device for impartingpneumatic, hydraulic or mechanical pressure on a sample, such as, asyringe, a piston, a pump, a bladder, a vacuum and so forth. Thesyringe-like device 50 illustrated comprises a piston 52 that isslidingly and sealingly engaged with the inner wall of a cylindricalchamber 56. The syringe-like device 50 is operated by either depressingor pulling on handle 54 that is connected to piston 52 to induce apositive or negative pressure differential and push or pull a sample,respectively. In this illustrated embodiment, the means for inducing apressure differential on a sample to direct the sample to a testsurface, the syringe-like device 50, is adapted and arranged to induce anegative pressure differential on a sample and pull the sample throughthe device 100 as the handle 54 is extended. In at least one particularembodiment, the inner wall of a cylindrical chamber 56 is provided withridges 58, detents or other means of informing a user of the device thata particular position is reached and notifies the user to stop pullingon the handle for a short period of time so that the device or contentsof the device can perform a particular function, such as diluting orfiltering or lysing the sample.

The operation of a device of the present invention and a method ofperforming a diffraction-based diagnostic test will now be describedwith respect to detecting C-reactive protein (CRP), a biomarker thatindicates bacterial infection. Persons of skill in the art willrecognize that devices and methods of the present invention can beadapted and modified to perform other types of diagnostic tests,including diagnostic test that are not diffraction based, such as pHtests, lateral flow tests, or color strips, and to detect analytes otherthan CRP. FIGS. 5, 6 and 7 are cross-sectional views of the diagnosticdevice taken through line 3-3 of FIG. 2 in various stages of operationof the pressure-assisted means. The position of a liquid sample withinthe device in the various stages is illustrated by dashed lines.

A health-care professional or a non-professional may use the followingdescribed version of the illustrated device to detect CRP in blood anddetermine if a person from whom a blood sample, or possibly another typeof sample, is obtained is suffering from a bacterial infection. With thehandle 54 in the unextended position illustrated in FIG. 1, a volume ofblood, for example a drop of blood, is contacted to the collection padand opening 22. Once the sample has contacted the collection pad, handle54 may be extended to Position 1 as illustrated in FIG. 5. The volume ofblood is then drawn from the collection pad, through opening 22 and intochannel 24 by the vacuum created when handle 54 is moved from a closedposition to Position 1. In FIG. 5, the sample 60 is illustrated enteringoptional chamber 34. Optional chambers may be included to provide forvarious functions. For example, chamber 34 may be provided in the deviceto include a filter for removing one or more undesirable components froma sample, a diluent to lower the viscosity of and thus increase the flowof a sample through the device, or to contain a reactant, an additive orother useful composition. In a desired embodiment, the diagnostic deviceincludes a means for diluting a sample, for example a diluent, inchamber 34. In this desired embodiment, chamber 34 may contain a diluentor any other composition that may be used to dilute, dissolve orotherwise react with one or more components in a sample or to performanother desirable function on a sample so that the sample is affected insome manner that provides more reliable test results for the analytebeing tested. Sample contacts the means for diluting a sample 34 viachannel 24 when handle 54 is extended to Position 1.

The device may be further provided with yet another optional chamber 36.Chamber 36 may be provided in the device to include a filter forremoving one or more undesirable components from a sample, a diluent tolower the viscosity of and thus increase the flow of a sample throughthe device, or to contain a reactant, an additive or other usefulcomposition. In a further desirable embodiment, the diagnostic deviceincludes a means for separating one or more components from a sample inchamber 36. Examples of means for separating one or more components froma sample include a membrane, filter media, porous films, nonwoven films,paper, etc. Such means for separating one or more components from asample may be used to remove one or more components from a sample thatare undesirable or that may adversely affect testing. For example, itmay be desirable to remove red blood cells from a blood sample viafiltration, lysing or agglutination. Removal of red blood cells from asample may improve the function of diagnostic devices and methodsbecause red blood cells may interfere with the analyte binding orotherwise associate with the printed binder; thus, removal could improvetest accuracy. The means for separating one or more components from asample may be general and remove a component or components based on aparticular property, for example, size or molecular weight. Or, themeans for separating one or more components from a sample may bespecific to a particular component, for example a bilirubin-bindinglayer may be included to remove bilirubin. Sample is further directedthrough channel 24 and into chamber 36 by extending handle 54 toPosition 2. Position 2 is illustrated in FIG. 6. In Position 2, thesample is illustrated as contacting the test surface 44. However, thenumber of positions may vary and the location of the sample within thedevice may vary. Once the sample has contacted the test surface 44,handle 54 can be further extended, preferably fully extended, to removeexcess sample from the test surface so that the test surface can beread. Advantageously, if the volume of chamber is greater than thevolume of blood that is produced from a freshly lanced finger(approximately 25 μL) or greater than the average volume (for examplegreater than 50 μL or even greater than 100 μL)) the liquid sample canbe safely stored before the test strip 40 is removed from the device100. In a desirable embodiment, test strip 40 is removably attached tothe device 10 and can be snapped off of or otherwise removed from thedevice to be viewed or placed in an analyzer for viewing or interpretingthe results.

In another desirable embodiment, the device is provided with windowsand/or indicia, for example numbered windows 1, 2 and 3 illustrated inFIG. 8, to assist a user in operating the device. After placing a sampleon the touch pad 22, the user pulls handle 54 and aligns piston 52 withPosition 1 to pull a sample from the touch pad through channel 24 andinto the means for diluting a sample 34. Position 1 is illustrated inFIG. 5 and the sample is illustrated as dashed area. The sample may thenbe allowed to dilute, dissolve or otherwise react with a desiredcomposition in the chamber for a particular period of time. The devicemay contact one or more compositions in chamber 34 that can be used tomodify the sample in some manner. For example, a composition may beprovided to reduce the viscosity of the sample, dissolve solids in thesample, or add reactants or diffraction enhancing elements to thesample. Next, the user further pulls handle 54 to align piston 52 withPosition 2 to draw the sample further through channel 24, through themeans for separating 36 and into chamber 30. Position 2 is illustratedin FIG. 6. In this described embodiment, the sample has been dissolvedin a diluent and one or more desirable components have been removed fromthe sample before the sample contacts the binder-printed test surface44. Next, the user further pulls handle 24 to Position 3 to removeexcess sample from the test surface. Position 3 is illustrated in FIG.7. The test strip 40 may now be removed from the device 100 and observedor inserted into a reader to be interpreted.

Although FIGS. 1-10 illustrate a syringe-like device 50 as a means forinducing a pressure differential on a sample, one skilled in the artcould configure and construct a device that comprises a means forinducing a pressure differential on a sample that is not a syringe or asyringe-like device. Furthermore, one skilled in the art will appreciatethat the devices of the present invention may be configured andconstructed to comprise a means for inducing a pressure differential ona sample that uses a positive pressure differential instead of anegative pressure differential to push rather than pull a sample to thetest surface. Examples of means for inducing a positive pressuredifferential include a pump, a plunger, a piston as well as a syringe.The means for inducing a pressure differential may be used to eitherpull a sample from an opening 22 to a test surface 44 or to push asample from an opening 22 to a test surface 44 as long as the meansdirects a sample or a portion of a sample to the test surface so thatthe sample can be analyzed.

While various patents and other reference materials have beenincorporated herein by reference, to the extent there is anyinconsistency between incorporated material and that of the writtenspecification, the written specification shall control. In addition,while the invention has been described in detail with respect to variousspecific examples, illustrations and embodiments thereof, it will beapparent to those skilled in the art that various alterations,modifications and other changes may be made to the invention withoutdeparting from the spirit and scope of the present invention. It istherefore intended that the appended claims cover all suchmodifications, alterations and other changes.

1-34. (canceled)
 35. A method for testing a sample comprising: introducing a sample into the opening of a diagnostic device comprising a syringe having a piston, the diagnostic device further comprising a test strip removably attached to the diagnostic device housing, wherein the test strip defines a test surface; inducing a first negative pressure differential on the sample by engaging the syringe to position the piston to a first indicator, the first indicator positioned to correspond to a pressure differential that directs the sample through a first channel and into a first chamber; inducing a second negative pressure differential by engaging the syringe to position the piston to a second indicator, the second indicator positioned to correspond to a pressure differential that directs the sample from the first chamber to the test surface and thereafter removing an unreacted portion of the sample from the test surface, through a second channel and into a second chamber.
 36. The method of claim 35, wherein the test surface is a diffraction-based test surface.
 37. The method of claim 36, wherein the device further comprises diffraction-enhancing elements.
 38. The method of claim 36, wherein the test surface is defined by a polymer film or metal-coated polymer film.
 39. The method of claim 35, wherein the second chamber has a volume sufficient to contain the entire sample.
 40. The method of claim 35, further comprising directing the sample from the opening through a third channel and into a third chamber located upstream of the first chamber, the third chamber in fluid communication with the first channel.
 41. The method of claim 40, wherein the third chamber comprises a means for separating one or more components from the sample comprising a filter, membrane, film, nonwoven, paper, precipitating agent, cell lysing agent, or combination thereof.
 42. The method of claim 41, wherein the means for separating one or more components from the sample removes red blood cells from the sample.
 43. The method of claim 40, wherein the third chamber comprises a means for diluting the sample comprising a diluent.
 44. The method of claim 40, wherein the diagnostic device further comprises a third indicator corresponding to a third piston position that indicates the sample has reached the third chamber.
 45. The method of claim 35, further comprising applying the test surface with an analyte-specific binder.
 46. The method of claim 35, wherein the first channel is formed by a capillary tube.
 47. The method of claim 35, wherein the sample is blood.
 48. A method for testing a sample comprising: introducing a sample into the opening of a diagnostic device comprising a syringe having a piston, the diagnostic device further comprising a test strip wherein the test strip defines a test surface; inducing a first negative pressure differential on the sample by engaging the syringe to position the piston to a third indicator, the third indicator positioned to correspond to a pressure differential that directs the sample through a third channel and into a third chamber; inducing a second negative pressure differential by engaging the syringe to position the piston to a first indicator, the first indicator positioned to correspond to a pressure differential that directs the sample from a third chamber through a first channel and into a first chamber; inducing a third negative pressure differential by engaging the syringe to position the piston to a second indicator, the second indicator positioned to correspond to a pressure differential that directs the sample from the first chamber to the test surface and thereafter removing an unreacted portion of the sample from the test surface, through a second channel and into a second chamber.
 49. The method of claim 48, wherein the test strip is removably attached to the diagnostic device housing.
 50. The method of claim 48, wherein the test surface is a diffraction-based test surface.
 51. The method of claim 50, wherein the device further comprises diffraction-enhancing elements.
 52. The method of claim 50, wherein the test surface is defined by a polymer film or metal-coated polymer film.
 53. The method of claim 48, wherein the second chamber has a volume sufficient to contain the entire sample.
 54. The method of claim 48, wherein the third chamber comprises a means for separating one or more components from the sample comprising a filter, membrane, film, nonwoven, paper, precipitating agent, cell lysing agent, or combination thereof.
 55. The method of claim 54, wherein the means for separating one or more components from the sample removes red blood cells from the sample.
 56. The method of claim 48, wherein the third chamber comprises a means for diluting the sample comprising a diluent.
 57. The method of claim 48, further comprising applying the test surface with an analyte-specific binder.
 58. The method of claim 48, wherein the sample is blood. 